The release of retrovirus particles from the infected cell is greatly stimulated by late domains present within the Gag precursor protein. Three distinct retroviral late-domain sequences have been identified: Pro-Thr/Ser-Ala-Pro (PTAP), Pro-Pro-x-Tyr (PPxY), and Tyr-Pro-x-Leu (YPxL). We played a key early role in identifying the PTAP late domain of HIV-1, and recent studies from our lab and others have demonstrated that late domains function by interacting with components of the multivesicular body (MVB) sorting machinery. We continue to be actively involved in elucidating the host cell machinery involved in the release of HIV-1 and other lentiviruses (e.g., EIAV and FIV) and have initiated studies aimed at identifying inhibitors of retrovirus budding. [Corresponds to Freed Project 2 in the April 2007 site visit report of the HIV Drug Resistance Program]